Chapter 6 Catabolism of proteins and metabolism of amino acids

1.1 SacchacridesLipidsProteinsEnergetic and structural materialFunctional material

1.2

Dietary proteins are digested into amino acids in the gastrointes-tinal tractPepsintrypsin, Chymotrypsin,and exopeptidasesAmino acids

1.3 Pepsin cleaves polypeptides into smaller peptides in stomach (N-terminal side of Y, F, W residues).Trypsin (C-terminal side of K, R) Chymotrypsin (C-terminal side of F, W, and Y) further cleave the peptides in small intestine.Elastase (C-terminal side of V, L, S, A) Carboxypeptidase (C-terminal side) and aminopeptidase cleave the small peptides into amino acids.

Acute pancteatitis

1.4 20041062004---

2004- 2004 2004-

1.4 (ubiquitin)()ATP

2.1

CO2 NH3 -CO2 + H2OCO2 + H2O

2.2

2.2.1 2.1.1.1 FAD2R-CH-COO- + 2O2 2H2O 2R-C-COO- + 2NH4+ + 2H2O2NH3+O2H2O + O2O2

2.2.1.1 L-pH 10D-GlyD-Asp

2.2.1.2

2.2.2

2.2.3 1LysPLPpyridoxal phosphate (PLP)

(Pyridoxal phosphate)Pyridoxal phosphate (PLP), being the prosthetic groups for all the aminotransferases, act as a temporary carrier of the amino groups.PLP accepts and then donates an amino group by forming a Schiff base with the amino-donating amino acid and amino-accepting a-keto acid (being a-ketoglutarate in many cases )respectively.

The reaction occurs via a typical ping-pong mechanism: the first product leaves before the second substrate enters.PLP facilitates transamination, racemization, decarboxylation of amino acids

KetiminePLP accepts and donates amino groups in the activesite of aminotransferases

There are different aminotransferases, each catalyzes the transfer of the amino group from an amino acid to a-ketoglutarate to form Glu and a new a-keto acid.Two important aminotransferases: aspartate aminotransferasesalanine aminotransferases

Aspartate aminotransferase (dimeric)PLP

Alanine-glucose cyclePyruvate is produced from muscle glycolysis and can take an amino group (from Glu) to form Ala.

Alanine-glucose cycleAlanine once gets to liver will then transfers its amino group to a-ketoglutarate or oxaloacetate to reform pyruvate.

The alanine-glucose cycle can continuously provide glucose to skeletal musclesAlanine-glucose cyclePyruvate is reconverted to glucose via the gluconeogenesis, then will be transported back to muscle.

2.2.4 L-D-D-L--

2.2.4 ---NAD(P)HH+ + NH3NAD(P)+ + H2OL-10L-

2.2.4 ----NADHH+NAD+H2ONH3GTPGDP + PiH2O

2.3 CO2

CO2--

The fates of products produced in general breakdown of amino acids-keto acidsamonia

3.1 -

TCA

3.1.1 -

-

---

3.1.2 -TCA

The carbon skeletons of amino acids are oxidized via the citric acid cycle

3.1.3 -TCACoA

-CoASuccinyl-CoAFumarateParuvate

3.2 < 0.1 mg/100mL;-CoATCA

3.2 :

3.2.1

Gln, Asn

;ATP

Serine

3.2.2

AnimalWaste products Aquatic animalsNH3Gln lyaseMost terrestrial vertebrateUreaUrea cycleBirds and terrestrial reptilesUric acidCatabolism of purinespiderGuanineSome fish Oxydized trimethyl-amine

Hans Krebs, Kurt Hehseleit (1932)Arginase

N-AGA

COOH CH2 CH2HC-NH-C-CH3 COOHO COOH CH2 CH2HCN COOHOHCO3-ATP ADP + PiC-CH3COO-NH4+ATPADP N-N-NH2-C-O-P-O-OOO-

Arg

Arg

TCA

Hepatic coma GluGlnGluTCA-TCATCA

4.1

One Carbon Unit

Predominantin animalsPredominant in bacteria

S-S-FH4

4.2 4.2.1

CH2=CCOOHNH2CH2-CCOOHNH2H2SCH2-CHCOOHNH2CH2-CCOOHOO2SOOHNH3NH3SOOHSO2CH2-CHCOOHNH2CH2-CH2NH2O2SOOHCO2HOOS-

4.2 4.2.2 CoA

4.3 PheTyr

Trp4

TyrosineTryptophan5-

5.

Synthesis of Amino Acids5.1 NH3NH3NH3NO3-NH3NH3

5.1.1 N2NH3N216ATP

5.1.2 NO3-NH3NH3NAD(P)HH+ + NO3- NAD(P)+ + NO2 - + H2O (FADH2)3NADPHH+ + NO2- + H+ 3NADP+ + NH3 + 2H2ONO3-

5.2

5.3

5.4

-Lysine()

PEP

3-p-

5-p-His

5.5

6. R NH C=NH2H2NNADPHH+ NADP++ 2O2 R NH C=N-OHH2NH R NH C=OH2N NO?

2. S-S-

3.

CCCH2CHCO

HN+ NH +NH3

ONH3 CCCH2CH2CO

HN+ NH

OH2OHO= CCCHCHCO

HN+ NH

OH2O CCCH2CH2CO

NH

OHO-O+NH2CHN-FH4GlutamateN5--FH4N5,N10--FH4NH3